CONTACT: BECKY SOGLIN
Iowa City IA 52242
(319) 335-6660; fax (319) 384-4638
Release: Dec. 17, 2002
UI cancer researchers receive grants to 'translate' findings into applications
University of Iowa researchers have received Translational Development and
Clinical Trials Seed Grants for prostate cancer and breast cancer investigations.
The one-year, $10,000 awards were made Dec. 1 through the Holden Comprehensive
Cancer Center at the UI.
These awards help faculty develop translational projects, which are investigations
that involve transferring basic research findings into practical applications
that may be tested through clinical trials.
Thomas Griffith, Ph.D., UI assistant professor of urology, received support
to investigate a gene-transfer approach as a potential alternative to the
invasive surgery that many prostate cancer patients currently receive as treatment.
Susan Roman, D.O., UI assistant professor of internal medicine, was awarded
support for the investigation of a drug combination treatment for patients
with advanced breast cancer.
Griffith's study aims to introduce a gene into prostate tumor cells so that
they will die off through a natural process known as apoptosis. The specific
gene is TNF-related apoptosis inducing ligand (known as TRAIL/Apo-2L), and
it signals, or "turns on," apoptosis. An adenovirus, which is a
disabled viral delivery vector, would be used to deliver the gene into targeted
In preliminary tests, TRAIL/Apo-2L caused a variety of tumor types to die,
yet did not harm normal tissues. The gene also is known to suppress tumor
growth through apoptosis in mice that have been implanted with human tumors.
Griffith and colleagues then found similar effects by introducing the gene
into prostate tumor cells and normal prostate cells in tissue cultures and
animal models. The UI Gene Transfer Vector Core contributed to the effort
by producing the TRAIL/Apo-2Lcontaining adenovirus.
Griffith's team now will test this laboratory-grade vector when it is combined
with other prostate cancer treatments such as chemotherapy and immunotherapeutic
strategies. The study will be done in tissue cultures and animal models.
The next step for the researchers then will be to evaluate the gene therapy
in patients, once institutional and federal approval is given for a clinical
study. That investigation will use a clinical-grade vector produced by a company
"Everything we have done so far in the lab has been designed to move
this particular vector into the clinic and test it in men with prostate cancer,"
Griffith said. "We will then see if we get the same kind of activity
in people that we get in the animal models, which is the destruction of tumor
cells. We also hope that the dead tumor cells will help activate the immune
system and initiate an anti-tumor response."
Roman's study will investigate the combination of docetaxel, a chemotherapy
drug, and lovastatin, a blood cholesterollowering drug, as a potential
treatment for advanced breast cancer.
"Docetaxel, which is also known as Taxotere, is one of the most effective
drugs in the treatment of advanced breast cancer. Unfortunately, not all patients
treated with this drug will have a shrinkage in their tumor, or the response
may be short-lived," Roman said.
Roman and colleagues hypothesize that the addition of lovastatin may strengthen
the effects of docetaxel without adding many harmful side effects. Advanced
breast cancer is a cancer that has spread (metastasized) and is difficult
to treat or has recurred but cannot be treated surgically or by other means.
The study builds on research undertaken by Roman and co-workers since she
joined the UI faculty earlier this year. Sarah Holstein, a student in the
UI Medical Scientist Training Program, previously demonstrated that lovastatin
adds to the anticancer activity of paclitaxel (Taxol), a drug that is related
to docetaxel. Holstein works with Raymond Hohl, M.D., Ph.D., UI professor
of internal medicine and pharmacology.
"Together, lovastatin and paclitaxel are more effective than either
drug alone, resulting in increased cancer cell death," Roman said. "Similarly,
we will now see if lovastatin will enhance the effects of docetaxel, which
has already been shown to be a very effective drug in treating patients with
advanced breast cancer. My laboratory data indicate that we will see synergism
Part of Roman's investigation, which uses human-derived breast cancer cells,
will be to study how the two drugs actually work together to inhibit breast
cancer cell growth.
Roman's team plans to open a clinical trial within the next months that
would target women with advanced breast cancer. The first part would investigate
the safety of the drug combination for patients with any type of solid tumor.
The second part would investigate optimal doses in women with advanced breast
"The beauty of the clinical trial is that we would use two drugs already
in clinical use, and that the addition of lovastatin to docetaxel may result
in few, if any, additional side effects," Roman said. "The hope
is that we are going to improve the anticancer effects of docetaxel without
adding harmful effects to the patient."
Griffith, Hohl and Roman are members of the Holden Comprehensive Cancer
Center at the UI, which is Iowa's only National Cancer Institute (NCI)-designated
comprehensive cancer center. NCI-designated comprehensive cancer centers are
recognized as the leaders in developing new approaches to cancer prevention
and cancer care, conducting leading edge research and educating the public
about cancer. Visit the center online at www.uihealthcare.com/depts/cancercenter